The zebrafish (Danio rerio) has proved to be an outstanding animal model to explore vertebrate development. Ongoing activities in the zebrafish research community have resulted in a multitude of resources available to researchers using this animal model. For example, (1) there is an International Zebrafish Stock Center and (2) a variety of antibodies and cDNA libraries are available. Furthermore, the extensive genetic characterization that zebrafish have undergone, including the creation of YAC genomic libraries and microsatellite genetic linkage maps, provide a cutting edge ability to rapidly take advantage of this animal model. This wealth of resources has been under exploited for evaluation of biology or pathophysiology of mature zebrafish. Most scientists evaluate zebrafish at the embryonic/larval stages after mutagenesis or toxin exposure. Thus, it is plausible that many mutations or toxin mediated effects that occur in late life will not be identified. It follows that a wealth of information with relevance to human biology and disease is being overlooked. The goal of the current project is to understand some aspects of the basic biology of aging zebrafish. To accomplish this, the following specific aims will be performed: 1) Characterize zebrafish demopraphy. Experienced zebrafish investigators estimate that the zebrafish lifespan is approximately two to four years. However, a critical evaluation of median and maximum lifespan has not been performed. These data are necessary for understanding the normal biology of zebrafish for comparative medicine purposes. The PI will evaluate lifespan parameters in wildtype and AB strains of zebrafish. Additionally, the effect of population density on lifespan will be evaluated. 2) Create an atlas of anatomy and age-associated histopathology of zebrafish. Evaluation of gross, histologic, and clinical pathologic changes that occur during aging in the zebrafish have not been systematically explored. To provide information about healthy animals and age-specific pathology, aging zebrafish will be euthanized at 6-month intervals for anatomic and histological, and pathological evaluation. These images will be collated into atlases that will be published and presented on the ZFIN Web site. 3) Demonstrate the utility of the mature zebrafish as an animal model for aging research. It is well established that the aging process diminishes mammal's ability to adapt to environmental stress. This is manifested, in part, by decreased heat shock protein (HSP) response to stress. Thus, the PI will test the hypothesis that HSP response is decreased in aging zebrafish. The PI will subject young, mature, and old zebrafish to both heat and ethanol stress and evaluate their mortality rates and their ability to activate HSP production. The PI also will assess the activation of the HSP70 promoter in fish transgenic for the HSP promoter driving the green fluorescent protein cDNA. When this project is completed, the PI will have established important baseline parameters that should allow mature zebrafish to be a powerful research tool for investigators whom explore research areas germane to a wide variety of NIH Institutes.